In the parent application it was discovered that isocoumarins and 3,4-dihydroisocoumarins could be prepared by the thallation and subsequent palladium promoted olefination of benzoic acid derivatives to provide a highly convenient new route to a variety of known biologically active compounds. In the process of the above referenced parent application, the starting material was either benzoic acid or a substituted benzoic acid. It has now been discovered that the basic process of that parent application can be expanded to conduct a very similar reaction with functionally substituted arenes to provide a variety of important oxygen and nitrogen heterocycles, namely certain ethers and lactones, isoquinolones, indoles and isocarbostyrils. All of these compounds are known to be of keen biological interest. For example, lactones are known to be odor bearing components of many plants, and as such have found wide industrial uses in the perfume industry. Certain lactones are also useful as solvents, paint removers, vapor sterilants and disinfectants. Isoquinolones are known to be useful in the manufacture of pharmaceuticals (such as nicotinic acid), insecticides, rubber accelerators, and anti-malarials. Indoles are known to be useful in perfumery, in agriculture and horticulture as growth enhancers, in some instances as flavorings, and indole alkaloids are known as especially physiologically active.
It therefore can be seen that there is a continuing need for the development of processes of preparing these useful compounds by a convenient and efficient synthesis.
It is a primary objective of the present invention to provide an improved one pot process for the preparation of certain ethers and lactones, isoquinolones, indoles and isocarbostyrils from functionally substituted arenes.
It is a further object of the present invention to prepare the above referred to oxygen and nitrogen heterocycles from simple olefins, dienes, allylic halides, vinyl halides, and unsaturated esters, by reacting functionally substituted arenes with an electrophilic thallium salt to provide an arylthallium intermediate compound which in turn is reacted with a palladium salt and the olefin, diene, allylic halide, vinyl halide, or unsaturated ester to provide the desired oxygen and/or nitrogen heterocyclic, such as an indole or an isoquinolone.
The method and manner of accomplishing each of the above objectives as well as others will become apparent from the detailed description of the invention which follows.